The purpose of this project is to explore the amino acids and their side-chain interactions in the environment of sulfhydryl and disulfide groups. Amino acid residues in these sites will be identified, in many cases after crosslinking a portion of peptide chain to a neighboring portion with a difunctional reagent. The effects of modification of amino acid residues on the enzymic, physical and chemical character of these sites will be determined. A particular modification which will be attempted will be the insertion of organic residues between the sulfurs of a disulfide resulting in distortion of the disulfide bridge. The effects of modification on the ability of enzymes to regain their native conformation after reduction of disulfide bridges will be tested.